The measurement of the function of nerves and nervous tissue by assessing their ability to transmit impulses provides valuable diagnostic information for the practice of medicine, surgery, chiropractic and other health fields and biological research. Metabolic, toxic, compressive and other types of nerve damage, the effects of interventions including pharmaceuticals and also nerve regeneration may be assessed using this information.
The nerve conduction velocity and amplitude evaluation traditionally utilizes electronic or electromagnetic stimulation of nervous tissue or nerve fibers to evoke a physiological response which is conducted along the length of the nervous tissue. This physiological response is recorded at a distant site on the nerve or the tissue innervated by this nerve such as muscle tissue. The nervous tissue response to this stimulus is recorded using an extremely sensitive electromagnetic amplifier. The distance between the site of stimulation and response recording is divided by the latency of the amplified recorded response time from the time of the stimulus to determine the Nerve Conduction Velocity (NCV) of this segment of the nerve. The amplitude of the recorded signal provides information regarding the actual number of nerve fibers responding.
Peripheral nerves are composed of individual nerve fibers if varying diameters. There are three major subpopulations of peripheral nerve fibers based on characterization of their fiber diameter. Any one of these subpopulations may become effected in a disease condition. Assessing the integrity of all three sub-populations or selectively stimulating these 3 populations of sensory nerve fibers is important for medical diagnostics, therapeutics and research purposes.
The nerves diameter also associated to its function. The largest diameter sensory nerve fibers are associated with sensation such as touch whereas the smaller diameter fibers are associated with pressure, temperature and pain sensations. The typical peripheral nerve is composed of large, middle and small diameter fibers that comprise <10%, <10% and >80% of the total number of fibers respectively. The larger the diameter of the nerve fiber, the greater its responsiveness to an electrical stimulus. The larger diameter nerve fibers have the fastest conduction velocity, the lowest electrical charge threshold and the shortest duration response signal (referred to as an Action Potential). A typical large diameter fiber has a conduction velocity of 50 m/s whereas a typical small diameter fiber has a conduction velocity of 1 m/s. The larger diameter fibers have greater numbers of ion channels per cross sectional surface area of exposed fiber in contrast with the smaller diameter nerve fibers which have the lowest number of ion channels per cross sectional surface area of exposed fiber. This difference in the cross sectional number of ion channels may contribute to the largest diameter fibers also having the briefest inter-response rest or refractory period of <0.4 msec in comparison to up to 20 msec in the smallest diameter fibers.
Presently existing technology for NCV evaluations utilizes a suprathreshold pulsed waveform of electrical or electromagnetic stimulus to evoke a nervous tissue response. A limitation of the presently existing technology is that it stimulates all of the nerve fibers in the peripheral nerve simultaneously.
Although the larger diameter nerve fiber comprises less than 10% of the typical peripheral sensory nerve's fibers, they make up >90% of the volume of the nerve. As a consequence of the large fibers comprising the bulk of the volume of the nerve, they contribute over >90% of the nerves response electrical potential from the combined Action Potentials (referred to as the Compound Action Potential, CAP) from all of the various diameter nerve fibers. The major contribution to electrical potential the CAP from the large diameter fibers drowns out the Action Potential signals from the smaller diameter fibers. As a result, the conventional NCV evaluation is limited in that it is primarily only capable of evaluating the function of the large diameter nerve fibers and at the same time because it stimulates all of the fibers in the nerve it is painful. Any medical test or procedure that is painful has poor patient compliance for initial and follow-up evaluations.
It is an aspect of the present invention to provide an electrical or electromagnetic stimulus that permits neuroselective NCV and amplitude measures to be obtained from the three major sub-populations of nerve fibers which will be much less painful and in-part painless in contrast with currently existing technology and result in superior patient compliance for evaluations than is possible using presently existing NCV technology.
It is also an aspect of the present invention to improve the therapeutic efficacy of interventions requiring precise nerve stimulation with or without nerve response monitoring equipment.
A pulsed waveform may be mathematically described by Fourier Analysis in terms of its harmonic components. These components may be described as related amplitude sine waves of specific harmonic frequencies. Previous research has demonstrated neuroselectivity of an electrical stimulus when it is administered in its harmonic components as a sinusoidal waveform as described in the following references:    1) Katims, J. J., Long, D. M., Ng, L.K.Y. Transcutaneous Nerve Stimulation (TNS): Frequency and Waveform Specificity in Humans. Applied Neurophysiology, Volume 49:86-91, 1986.    2) Katims, J. J. Electrodiagnostic Functional Sensory Evaluation of the Patient with Pain: A Review of the Neuroselective Current Perception Threshold (CPT) and Pain Tolerance Threshold (PTT). Pain Digest Volume 8(5), 219-230, 1998.
It is believed that the slow rate of depolarization of a low frequency (eg. 5 Hz) sinusoid stimulus permits the large diameter nerve fibers, due to their fast responsiveness, to repolarize faster than the this slow stimulus can polarize them. Therefore the low frequency sine wave stimulus is not sufficient to bring the large diameter nerve fibers to their threshold potential. The large diameter fibers have a refractory period as brief as 0.4 msec and a small diameter fiber can have a refractory period as long as 20 msec. A period of 180° of a 2000 Hz sinewave is 0.25 msec and a 180° period of a 5 Hz sinewave is 100 msec in duration. This is illustrated in FIG. 10. The low frequency sinewave is of sufficient charge and duration to depolarize the small diameter nerve fibers to their threshold potential which enables them to generate action potentials in response to this stimulus. This low frequency sinusoid waveform stimulus has such a slow rate of depolarization that the large diameter rapidly responding nerve fibers can repolarize faster than this stimulus can depolarize it. In contrast, a 2000 Hz sinewave is too fast and has a relatively lower charge than the 5 Hz sinewave (approximately 400× less charge per 180° of stimulus). The differences between these two different frequency sinusoid waveforms is illustrated in FIG. 10.
Nervous tissue stimulation technology currently commercially available that is used for purposes of obtaining NCV measurements utilizes a square or pulsed waveform stimulus which, in contrast to a sinusoid or slowly rising waveform, has an almost instantaneous change in polarization. The most widely used methodology for conducting NCV studies routinely administers the stimulation at 150% of the intensity required to evoke a maximal response as observed using a response monitoring apparatus. This intensity this 150% supramaximal response stimulation causes a rapid change in the nerve tissue polarization and excites all the subpopulations of nerve fibers at the same time and therefore lacks the neuroselectivity of the sinusoid waveform of specific frequencies.
My previous patents, U.S. Pat. No. 4,503,863, No. 4,305,102, and No. 5,806,522 describe a “Method and Apparatus for Transcutaneous Electrical Stimulation” using a continuous (i.e. of a duration over 0.5 seconds, much greater than 360° of a sinusoidal waveform constant alternating current stimulus of various frequencies for purposes including the determination of the neuroselective Current Perception Threshold (CPT) measurements using a non-invasive, non-aversive electrical stimulus applied at various frequencies. Work has continued in this direction endeavoring to develop this technology to construct a neuroselective nerve conduction velocity device. The technology described in these above cited CPT related patents was not compatible with currently existing commercially available EMG devices. The problem was that after administering an alternating current stimulus to the skin for approximately 0.5 seconds or more and then turning off the stimulus to permit recording of the nerves response, a voltage potential remained in the subjects body and drowned out the possibility of recording any nerve response from the response monitoring electrode. The reason for this voltage potential remaining on the subject is that there are inductive reactance properties of human skin which result in the applied voltage and current going out of phase.
It was necessary in the development that ensued leading up to the present invention to develop entirely new type electrodiagnostic apparatus for neuroselective of nerve stimulation. Examples of prior art nerve conduction electrical or electromagnetic response stimulator patents include the following are set out below:
Inventor(s)U.S. Pat. Nos.U.S. PatentsIssue Date4,807,643RosierFeb. 28, 19895,066,272Eaton, et al.Nov. 19, 19915,143,081Young, et al.Sept. 1, 19925,806,522KatimsSept. 15, 19985,976,094GozaniNov. 2, 1999